Silicosis is a chronic inflammatory and fibrotic lung disease resulting from inhalation of crystalline forms of silicon dioxide. The investigations of this Project form an integrated, collaborative approach that will address several aspects of the events initiated by silica particle-lung cell interactions which then lead to injury, inflammation, and subsequent fibrosis. We hypothesize that the initial interactions of silicon dioxide particles with biological molecules and cells determine the degree and nature of the lung response, and that these interactions are primarily a function of specific particle surface properties. Subsequent events and the development of chronic lung pathology are determined both by the continued presence of particulates and by the functions of the inflammatory and immune cells recruited to the lung. This Project will focus on studies of cellular responses in the lungs of rate following exposure to silica. Our major goals are to assess the functions and interactions of pulmonary macrophages and lymphocytes in the evolution of silicosis in an animal model of aerosol exposure to two forms of silicon dioxide, cristobalite and quartz. These two forms of crystalline silicon dioxide are known to cause pulmonary disease in humans and experimental animals, but differ markedly in their degree of fibrogenicity. We will investigate the role of different subclasses of lymphocytes in the development of silicosis and a secretory product of activated macrophages, macrophage derived growth factor, (MDGF), believed to be involved in the development of fibrosis. Silicosis provides a model of chronic diffuse interstitial immunologic and fibrotic lung disease in which the cause is known. Further studies of silicosis will provide new insights into the mechanisms of this important occupational lung disease, better treatment for those who suffer from it, and better understanding of the mechanisms which govern pulmonary injury, inflammation, repair and fibrosis.